Phase 2 trial of neoadjuvant toripalimab with chemotherapy for resectable stage III non-small-cell lung cancer

Abstract

Multimodality treatment provides modest survival benefits for patients with locally advanced (stage III) non-small-cell lung cancer (NSCLC). Nevertheless, preoperative immunotherapy has continuously been shown to be promising in treating resectable NSCLC.This phase 2 trial enrolled patients with AJCC-defined stage IIIA or T3-4N2 IIIB NSCLC deemed surgically resectable. Patients received three cycles of neoadjuvant treatment with intravenous PD-1 inhibitor toripalimab (240 mg), carboplatin (area under the curve 5), and pemetrexed (500 mg/m2 for adenocarcinoma) or nab-paclitaxel (260 mg/m2 for other subtypes) on day 1 of each 21-day cycle. Surgical resection was performed 4-5 weeks afterward. The primary endpoint was major pathological response (MPR), defined as less than 10% residual tumor remaining at the time of surgery.Thirty-three patients were enrolled, of whom 13 (39.4%) had T3-4N2 stage IIIB disease. Thirty (90.9%) patients underwent resection and all except one (96.7%) achieved R0 resection. Twenty patients (60.6%) in the intention-to-treat population achieved an MPR, including 15 patients (45.5%) who achieved a pathological complete response (pCR). The MPR and pCR rates in the per-protocol population were 66.7% and 50.0%, respectively. The surgical complications included three cases of arrhythmias, one case of a prolonged air leak, and one case of chylothorax. The most common grade 3 treatment-related adverse event (TRAE) was anemia (2, [6.1%]). Severe TRAEs included one (3.0%) case of grade 3 peripheral neuropathy that resulted in surgical cancellation.Toripalimab plus platinum-based doublet chemotherapy yields a high MPR rate, manageable toxicity, and feasible resection in stage III NSCLC.Trial ClinicalTrials.gov (NCT04304248).

Keywords: Lung cancer; chemotherapy; immunotherapy; neoadjuvant; toripalimab.

Conflict of interest statement

No potential conflict of interest was reported by the author(s).

© 2021 The Author(s). Published with license by Taylor & Francis Group, LLC.

Figures

Figure 1.

Radiographic findings and pathologic response following neoadjuvant toripalimab plus platinum-based doublet chemotherapy in the intention-to-treat population. TPS, tumor proportion score; CR, complete response; PR, partial response; SD, stable disease; PD, progressive disease; LELC, lymphoid epithelial-like carcinoma

Figure 2.

A) Correlation between radiographic findings and pathologic response (each point indicates a single patient) CR, complete response; PR, partial response; SD, stable disease; b) maximum standardized uptake value (SUVmax) at baseline and before the operation (each line indicates the change in the SUVmax in a single patient); and c & d) the representative immunohistochemistry images of paired baseline biopsies (top) and post-treatment (bottom) sections stained with H&E, and antibodies targeting CD19, CD8 and Granzyme B respectively for two patients who achieved pathological complete response (pCR, c) and major pathological response (MPR, d), black scale bars = 100 μm